(1) Field of the Invention
This invention relates to a system for the administration of drugs and/or biologically active materials by infusion. More particularly, this invention relates to a delivery device in which the gradual reduction of a liquid volume in a control chamber serves as a slow braking device, thus limiting the infusion rate of the drugs or other materials being infused. The reduction of liquid volume may be achieved by chemical or electrical conversion of part of said liquid to a gas which is released to the environment. A pressure-application means such as a spring drives the infusion of the drugs and/or biologically active materials at a controllable and stable rate in accordance with the steady reduction of liquid volume. Where the conversion of liquid to gas is due to electrolysis, the rate of the electrolysis process (for example the production of hydrogen and oxygen from water) is controlled by an electric current. This current is supplied by a battery and can be activated and controlled by an electronic timer or a biomedical control system which reacts to stimuli related to bodily functions, such as temperature, pH, a glucose sensor, muscle contractions, electroencephalography, or electrocardiography, and/or a combination of the above.
(2) Description of Related Art
There have been many approaches to meet the problems of regulating the delivery of drugs and/or biologically active materials (hereinafter collectively referred to as “drugs”) in the place and at the proper dose to achieve the desired regulatory effect. Some of these systems depend on the utilization of physical or chemical stimuli which are a result of changes in the biological systems. Such stimuli may include externally measured bodily functions such as temperature, muscle contractions, electroencephalography, electrocardiography; chemical or biological sensors monitoring liquid excretions from the skin, or invasive or minimally invasive sensors to measure various analytes within the body. U.S. Pat. No. 5,820,622, hereby incorporated by reference, describes an exemplary approach to controlling the flow-rate of a drug-delivery device based on input from a sensor needle inserted into the subject's body. The sensor needle uses an enzymatic detector to detect an analyte such as glucose in the subject's plasma, and thereby determine the desired flow-rate of the drug.
The primary delivery methods for drug infusion are infusion pumps utilizing gravity flow and other electrically driven mechanical pumps (peristaltic or syringe pumps) attached to syringes or intravenous tubing which infuse the drugs into the body. In addition, elastomeric balloons can also be utilized as the contraction force. However, all these systems require large, complicated supports along with electronic or mechanical pumps which restrict their portability for ambulatory patients in hospitals or at home.
For ambulatory use there are two main approaches: (1) An electric motor or solenoid drive apparatus connected to a lead screw mechanism which compresses a piston to drive the infusion, and (2) A gas-driven method where the gas generated drives the infusion, generally via a movable membrane or piston-driven pumping chamber. The former approach is extensively described in the prior art, for example in U.S. Pat. No. 4,562,751 and U.S. Pat. No. 4,678,408 and is exemplified by the “MicroMed” product from Medtronic Minimed Inc. (Northridge, Calif.). In these devices, torque is translated to drug pressure and, as a result, the mechanism is very sensitive to friction and thus demands very tight manufacturing tolerances. Moreover, whereas the lead screw method is very accurate and reliable, it is too expensive to be used as a disposable product. Accordingly, the products of this nature suffer from the disadvantage that they require filling “in the field” and the manufacturers are required to provide a maintenance infrastructure. Given the medical importance of the devices, this maintenance becomes a critical issue. Accordingly, much effort has been devoted to the development of inexpensive, disposable ambulatory infusion devices, as described below. The advantage of such a device would be that it would come pre-filled with the drug and, if for whatever reason it malfunctioned, the patient could simply replace it with a further unit.
The prior art describes a number of such disposable devices, which typically employ a gas-driven infusion principle. U.S. Pat. No. 5,318,557 and U.S. Pat. No. 5,527,288 describe an inexpensive, gas-driven infusion device which can be manufactured sufficiently inexpensively in order to constitute a disposable product. The embodiments described therein employ an electrolytic cell for gas production as per U.S. Pat. No. 5,062,834. A similar gas-driven device is described in U.S. Pat. No. 5,354,264. This device utilizes gas pressure from free oxygen and hydrogen derived from the electrolysis of water at the electrodes in negatively charged polymeric hydrogels. Said device ensures that the gas generated remains within the walls of the gas chamber by making said walls “rigid and impermeable to gases”. In all these devices, the gas pressure forces the infusion of the drugs through appropriate means into the body, with the pressure being dependent on the rate of electrolysis, which is in turn controlled by an electric current. A further class of devices uses the same gas-driven principle, but generates this gas by chemical rather than electrical means. For example, U.S. Pat. No. 5,814,020, hereby incorporated by reference, describes a gas-powered infusion device where the gas is generated either by an electrolytic cell or by the reaction between citric acid and sodium bicarbonate; said reaction generating carbon dioxide and water.
The central problem with these gas-driven devices is that they all employ a gas-filled chamber in order to drive the drug infusion. As gases are very susceptible to changes in ambient temperature and air pressure, the danger of employing this principle is that a significant and undesirable change in the flow-rate will occur as such temperature or pressure changes occur. For example, a loss of pressure in an airplane could result in a sudden bolus being delivered at an inappropriate time. Similarly, a drop in temperature could result in the drug infusion stopping. For these reasons, despite massive development efforts, these products have faced considerable commercial obstacles to implementation. The prior art confirms the problematic nature of this issue: In a partial attempt to address this issue, U.S. Pat. No. 6,186,982 describes a flow-regulation chamber appropriate to the above-described devices which attempts to compensate for such temperature and/or pressure changes. Nonetheless, this issue of heat and pressure sensitivity is an inherent disadvantage inhibiting the commercialization of these products.
The prior art further describes a number of options for attachment of needles to such ambulatory infusion devices. In addition to the standard method of having the infusion device connected via a tube to the hollow needle, U.S. Pat. No. 5,527,288 describes the attachment of a rigid needle to the underside of the diffusion device such that adhesion of the device to the skin causes the needle to penetrate the skin; and U.S. Pat. No. 5,599,438 describes a similar device but with the addition that the needle is auto-injected into the skin after device attachment.